CELL THERAPIES

Combined Cartilage cell therapy and Meniscus replacement: An improved Biological reconstruction? 

AN INVESTIGATION INTO PATELLOFEMORAL PAIN: IMPROVING DIAGNOSTICS, PROGNOSTICS AND CELL-BASED THERAPIES

Larissa Rix, Martyn Snow, Jan Herman Kuiper, Andrew Barnett, Karina Wright

Funded by the Orthopaedic Institute

A common disorder seen in orthopaedic clinics is patellofemoral pain (PFP) (see picture insert 1). PFP affects the patellofemoral joint (PFJ), which is made up of the kneecap, known as the patella, and the trochlea groove, of which the patella sits in. PFP typically presents in patients ranging from young and active to sedentary or elderly. Symptoms often occur as pain behind the patella with increasing activity such as squatting, stair climbing or kneeling. With the exact cause of PFP being unknown, diagnosis and treatment are difficult, with most treatment aimed at physiotherapy to target muscle imbalances, or surgical intervention to combat alignment issues. However, when left untreated, PFP can develop into patellofemoral osteoarthritis (PFOA), which occurs when the cartilage breaks down on the surface of the patella, trochlea, or both. At early PFOA, cartilage therapy such as autologous chondrocyte implantation (ACI) can be used to treat the damaged cartilage. Otherwise, at later stage PFOA, the only treatment option is a partial or total knee replacement. Therefore, this PhD project aims to better understand the biology of PFP, and the PFJ, in order to better the diagnosis and treatment of the disorder.

Currently, the main method for assessing cartilage damage is through the use of radiological imaging. Most knee cartilage lesions are diagnosed using magnetic resonance imaging (MRI). However, MRI scans misdiagnose around 20% of cartilage lesions, making it not a highly sensitive tool. Therefore, we assessed how well another method, known as single-photon emission computerised tomography with conventional computer tomography (SPECT/CT), could diagnose cartilage lesions. SPECT/CT works by tracking a radioactive dye to the site of cartilage injury on a SPECT scan and combining the image with a CT scan. This allows the visualisation of the area of cartilage breakdown. Literature around cartilage lesion diagnosis on SPECT/CT was evaluated and we concluded that SPECT/CT may be a useful tool for the detection and localisation of cartilage lesions, particularly in cases where there is an absence of lesions on other imaging tools, or a lack of correspondence with patients’ symptoms.

Furthermore, to improve the treatment of cell-based therapies, we have assessed 121 patients who underwent ACI treatment of the PFJ to identify risk factors which influence outcome of ACI. Results showed that factors such as age at time of ACI, the location of the lesion within the PFJ, and the number of cells implanted into the lesion all significantly influenced the outcome of ACI after 1 year.

To further our understanding of PFP and the knee joint of those with PFP, we will undertake regional difference assessment of the knee of patients with PFP undergoing total knee replacement compared to those without PFP in respect to histological landmarks (see picture insert 2), gene assessment and cartilage matrix assessment. To improve diagnostic and prognostic indicators of PFP, we will assess the synovial fluid of patients treated with ACI in the PFJ to establish biological indicators of the disorder, with the hope to diagnose and treat the disorder at early onset.

The anatomy of the knee, showing the origins of patellofemoral pain (PFP)

Knees of patients with and without patellofemoral pain (PFP) for comparison in this project

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